Action Points

Children with lower baseline height z-scores experience the greatest improvement in height z-scores after 2 years of etanercept treatment.

In severe juvenile idiopathic arthritis (JIA), which can restrict and delay children's growth, etanercept (ETN) therapy is associated with improved height z-scores over the first 2 years of treatment, according to a British cohort study published online Jan. 30, 2015, in Rheumatology.

Furthermore, children not receiving corticosteroids experienced even greater height improvement following ETN anti-TNF therapy, reported the investigation headed by Lianne Kearsley-Fleet, MSc, research assistant, Arthritis Research UK Centre for Epidemiology at the University of Manchester in England.

The analyzed study sample consisted of 191 ETN-treated children (65% female) out of 668 pediatric patients under age 16 registered by Nov. 28, 2011, in the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR-ETN), started in 2004 and involving 42 centers. Children's median age at baseline was 11.0 years (interquartile range [IQR] 7.3-12.9), and median disease duration was 3.5 years (IQR 1.7-7.1).

More than half (58%) were on concomitant methotrexate and 38% were on concurrent oral corticosteroids (76% in systemic arthritis, 32% in nonsystemic arthritis).

Mean heights were recorded at baseline and at years one and two. Height z-scores were calculated according to World Health Organization (WHO) standards for age and gender, and changes in z-scores were documented over time. Patients' mean height z-score at baseline was -74 (SD1.4) compared with the population reference median. Twenty-nine patients (15%) were classified at baseline as having short stature.

After 1 year on ETN, mean height z-scores improved to -0.57 (SD1.4) and at 2 years to -0.45 (SD 1.4), for an overall change of +0.29 (P < 0.001). Factors associated with improvement included lower baseline height (-0.110 per unit, 95% CI minus 0.161-minus 0.059, P<0.001), as well as no oral corticosteroid use at baseline (-0.192, 95% CI minus 0.343-minus 0.040, P=0.013). The mean height z-score, however, remained lower than that of the WHO comparison population.

After 2 years, the number of patients classified as having short stature dropped to 18 patients (9%); 13 (7%) were classified as having poor growth. Mean height velocity was 5.8 cm/year (SD 2.4), and, interestingly, many patients demonstrated greater height velocity than age- and gender-matched peers. Patients with systemic arthritis had the lowest mean height z-scores after 2 years: -1.45 (SD 1.3).

Since the strongest association for height improvement was with baseline height z-score, Kearsley-Fleet and colleagues suggested that perhaps "patients with the most severe growth restriction prior to ETN had a greater capacity for growth and were able to gain from treatment. However, this could also be explained by regression to the mean."

The authors also noted a weak association between growth rate improvement and the pubertal 11 to 14 age group.

As for concurrent corticosteroid treatment, which was administered mainly to patients with systemic arthritis, they said, "This could indicate that oral corticosteroid use at baseline is a marker of disease severity. It could also highlight the growth inhibitory effects of using corticosteroids in children."

Study limitations noted by the authors include the low number of patients given regular height measurements. "Due to the observational nature of this data collection, it was not possible to ask patients to attend additional appointments, as this may have contributed to an element of selection bias," they said.

Other drawbacks include the lack of access to pubertal data, which is important for understanding growth, and the international, multi-ethnic nature of the WHO reference population, which may differ from that of the U.K.

Additional follow-up will be needed to address the effects of ETN therapy on adult height. "Further analyses of children who have received ETN more recently, where more aggressive, early therapy is advised, might reveal additional insights into the relationship between control of inflammation and growth velocity," the authors concluded.

No specific funding from any source was received to carry out the research in this article. The BSPAR-ETN study is funded by a research grant from BSPAR to the University of Manchester. Two of the authors declared medical education funding or honoraria from pharmaceutical companies for work unrelated work.